CCTG 595 is a controlled, open-label, two-arm, randomized (1:1) clinical demonstration project to determine if the use of a text-message based adherence intervention (iTAB) improves retention and adherence to PrEP compared to standard of care (SoC) PrEP delivery.

CCTG 595 will compare adherence to fixed dose TDF/FTC, between subjects randomized to receive SoC plus text message reminders versus SoC, when used for pre-exposure prophylaxis among MSM at high risk for HIV acquisition.

The primary outcome is defined as a composite endpoint of remaining on PrEP and having adherence > 90% over 48 weeks of follow-up. The adherence endpoint will be derived from the 4 day ACTG adherence assessment from each of the visits from week 4, 12, 24, 36, and 48. 'Adherent' will be defined as self-reported TDF/ FTC adherence of 90% or greater (at least 18 of 20 days). If a subject misses an adherence assessment within the window of a scheduled visit or discontinues study prior to week 48, then the missed visits will be counted no adherence for the time of that visit. All randomized subjects that were dispensed PrEP at baseline will be included in the modified intent-to-treat analysis.

Secondary Outcome Measures:

Adherence in subjects that remain on PrEP [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ] [ Designated as safety issue: No ]

Compare adherence to TDF/FTC in the iTAB versus SoC in the subjects that remain on PrEP (at 48 weeks and up to 2.5 years follow up) by the continuous measure of percent days adherent by the cumulative 4 day ACTG and the visual analog scale (VAS) recall in an 'as treated' analysis.

Adherence to PrEP for duration of study [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ] [ Designated as safety issue: No ]

Compare adherence to TDF/FTC in the iTab versus SoC groups for the duration of the study (up to 2.5 years). Adherence will be compared using the same outcomes as the Primary Outcome Measure (self-reported to be on drug and 90% adherent and 100% detectable FTC at each scheduled visit) as modified intent to treat analysis.

Determine the factors associated with discontinuation of TDF/FTC at any time point including change in perceived and actual risk of HIV acquisition, demographics, ongoing substance use, untreated mental illness, socioeconomic status, low health/HIV and system literacy, fear of disclosure and non-English language.

Rate of HIV seroconversion [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ] [ Designated as safety issue: No ]

Determine the rate of HIV seroconversion in PrEP users and compare the iTAB to SOC arms for number of new infections as a proportion at 48 weeks and end of study.

Acquisition of other sexually transmitted infections [ Time Frame: Baseline to Week 48, and up to 2.5 years follow up if subject desires to remain on study after reaching the primary endpoint ] [ Designated as safety issue: No ]

Measure acquisition of other sexually transmitted infections (STIs); the proportion of subjects with any new STI at any site will be compared between the iTAB to SOC arms at 48 weeks and through the end of the study.

Changes in risk behavior [ Time Frame: Baseline until up to 2.5 years follow up ] [ Designated as safety issue: No ]

Evaluate changes in risk behavior after initiation of PrEP (risk compensation) comparing baseline to subsequent visits for number of HIV positive/unknown status partners and any unprotected anal intercourse with an HIV positive/ unknown status partner.

Safety and tolerability of daily TDF/FTC [ Time Frame: Baseline until up to 2.5 years of follow up ] [ Designated as safety issue: No ]

Evaluate the safety and tolerability of daily TDF/FTC given for PrEP including discontinuation for any adverse event, serious adverse events and adverse events (grade 2 or higher).

Other Outcome Measures:

Changes of self-reported adherence [ Time Frame: Baseline until up to 2.5 years of follow up ] [ Designated as safety issue: No ]

Describe changes over time of self-reported adherence in real time by texting.

This proposal will perform a study of potential methods to improve adherence and retention by evaluating standard procedures versus the use of the iTAB platform.

All subjects will receive SoC that will include health education, clinical assessments, laboratory safety monitoring, STI and HIV screening, HIV risk reduction counseling, assessment of psycho-social barriers, adherence counseling, and completion of a computer based survey.

Active Comparator: SoC + iTab

Subjects assigned to the iTAB intervention will receive daily dosing reminders that will be sent for the first 6 weeks and then continue with reminders for the duration of the study.

Subjects will have visits with the study coordinator to introduce the iTAB texting system.

Once the time is identified, the text reminder system is automated. Patients will confirm medication taking via text responses to the personalized reminders. If a participant does not respond on three consecutive occasions, a high alert message (chosen by the participant) will be sent. If the subject does not respond to this message, the study coordinator would initiate phone calls to contact the subject and explore barriers.

Device: SoC + iTab

Text messaging reminders to improve adherence to PrEP

Detailed Description:

A total of 400 HIV-uninfected men who have sex with men (MSM)and male to female (M to F) transgender individuals with recent high-risk transmission behavior will be enrolled into the study. Each subject will be followed for up to 48 weeks after enrollment of the last subject. The primary endpoint will be measured at 48 weeks.

All subjects will start PrEP with TDF + FTC fixed dose combination given once daily. Subjects will be randomized (1:1) to either the iTAB text messaging adherence reminder intervention with SoC or the SoC alone arm. Subjects placed into the iTAB intervention arm will receive a personalized, automated texting system to maintain adherence and retention. Both groups will receive access to PrEP in accordance with standardized comprehensive methods of prescribing, risk reduction counseling, adherence counseling, and clinical assessments that include safety monitoring, as well as HIV and STD screening.

TDF 300 mg + FTC 200 mg fixed dose combination will be given orally once daily starting at the baseline visit (month 0) and continued throughout the study.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Man or transgender M to F who has sex with men.

Age 18 years or older.

Subjects must have substantial ongoing risk of acquisition of HIV as evident by one or more of the following:

Has at least one HIV infected sexual partner for ≥4 weeks.

No condom use during anal intercourse with ≥3 male sex partners who are HIV-positive or of unknown HIV status during the last 3 months.

No condom use during anal sex with ≥1 male partner and STI diagnosis during the last 3 months.

Negative for HIV infection by rapid HIV test and confirmed negative by NAT or other sensitive method such as antibody- antigen test.

Ongoing systemic corticosteroids (with the exception of short courses of tapering steroid doses for asthma or other self- limited condition).

Interleukin-2 (IL-2)

Interferon (alpha, beta, or gamma)

Other agent known to have a significant interaction with TDF or FTC

Proteinuria 2+ or greater by urine dipstick

Signs or symptoms suggestive of acute HIV infection

Any other reason or condition that in the opinion of the investigator would interfere with participation, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01761643